Blepharophimosis, ptosis, and epicanthus inversus syndrome

Summary

Blepharophimosis, ptosis, and epicanthus inversus syndrome (MONDO:0007201) is a disease (an umbrella term covering 5 Mondo subtypes) caused by FOXL2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: FOXL2 (GenCC Definitive)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 138
• Phenotypes (HPO): 9

Clinical features

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000508	Ptosis	Very frequent (80-99%)
HP:0000581	Blepharophimosis	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0000545	Myopia	Frequent (30-79%)
HP:0011481	Abnormal lacrimal duct morphology	Frequent (30-79%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000664	Synophrys	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	blepharophimosis, ptosis, and epicanthus inversus syndrome
Mondo ID	MONDO:0007201
MeSH	C562419
OMIM	110100
Orphanet	126
DOID	DOID:14778
SNOMED CT	715391004
UMLS	C0220663
MedGen	66312
GARD	0000023
NORD	862
Is cancer (heuristic)	no

Also known as: blepharophimosis syndrome type 1 · blepharophimosis types 1 and 2 · blepharophimosis, epicanthus inversus, and ptosis, type 1 · blepharophimosis, epicanthus inversus, and ptosis, type 2 · blepharophimosis, ptosis, and epicanthus inversus · blepharophimosis, ptosis, and epicanthus inversus syndrome · blepharophimosis, ptosis, and epicanthus inversus syndrome type 1 · Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome · blepharophimosis, ptosis, epicanthus inversus syndrome · blepharophimosis, ptosis, epicanthus inversus with ovarian failure · blepharophimosis-epicanthus inversus-ptosis syndrome · BPES · BPES type 1 · BPES with premature ovarian failure

Data availability: 138 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › blepharophimosis, ptosis, and epicanthus inversus syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (5): blepharophimosis-epicanthus inversus-ptosis due to 3q23 rearrangement syndrome, blepharophimosis-epicanthus inversus-ptosis due to a point mutation syndrome, blepharophimosis-epicanthus inversus-ptosis due to copy number variations, blepharophimosis-ptosis-epicanthus inversus syndrome type 1, blepharophimosis-ptosis-epicanthus inversus syndrome type 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

138 retrieved; paginated sample, class counts are floors:

79 pathogenic, 30 likely pathogenic, 16 uncertain significance, 5 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 3 benign, 1 not provided, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
433554	Single allele	COPB2	Pathogenic	no assertion criteria provided
162043	NM_023067.4(FOXL2):c.142_173delinsGCGCT (p.Lys48_Ser58delinsAlaLeu)	FOXL2	Pathogenic	no assertion criteria provided
162044	NM_023067.4(FOXL2):c.965_983dup (p.Thr329fs)	FOXL2	Pathogenic	no assertion criteria provided
162045	NM_023067.4(FOXL2):c.843_859dup (p.Pro287fs)	FOXL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687548	NM_023067.4(FOXL2):c.775_778del (p.Thr259fs)	FOXL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1699241	NM_023067.4(FOXL2):c.340A>T (p.Lys114Ter)	FOXL2	Pathogenic	criteria provided, single submitter
1705491	NM_023067.4(FOXL2):c.768dup (p.Pro257fs)	FOXL2	Pathogenic	criteria provided, single submitter
180594	NM_023067.4(FOXL2):c.650C>T (p.Ser217Phe)	FOXL2	Pathogenic	criteria provided, multiple submitters, no conflicts
180596	NM_023067.3(FOXL2):c.661GCN[15_24] (p.Ala221[(15_24)])	FOXL2	Pathogenic	no assertion criteria provided
180598	NM_023067.4(FOXL2):c.841_857dup (p.Pro287fs)	FOXL2	Pathogenic	criteria provided, single submitter
180600	NM_023067.4(FOXL2):c.854del (p.Pro285fs)	FOXL2	Pathogenic	criteria provided, single submitter
2734577	NM_023067.4(FOXL2):c.223C>T (p.Leu75Phe)	FOXL2	Pathogenic	criteria provided, multiple submitters, no conflicts
3256534	NM_023067.4(FOXL2):c.684del (p.Ala229fs)	FOXL2	Pathogenic	criteria provided, single submitter
3366961	NM_023067.4(FOXL2):c.249C>A (p.Tyr83Ter)	FOXL2	Pathogenic	criteria provided, single submitter
369886	NM_023067.4(FOXL2):c.15C>A (p.Tyr5Ter)	FOXL2	Pathogenic	criteria provided, single submitter
369887	NM_023067.4(FOXL2):c.43del (p.Leu15fs)	FOXL2	Pathogenic	criteria provided, single submitter
369888	NM_023067.4(FOXL2):c.171C>G (p.Tyr57Ter)	FOXL2	Pathogenic	criteria provided, single submitter
369889	NM_023067.4(FOXL2):c.173C>A (p.Ser58Ter)	FOXL2	Pathogenic	criteria provided, single submitter
369893	NM_023067.4(FOXL2):c.205G>T (p.Glu69Ter)	FOXL2	Pathogenic	criteria provided, single submitter
369898	NM_023067.4(FOXL2):c.293G>A (p.Trp98Ter)	FOXL2	Pathogenic	criteria provided, single submitter
369907	NM_023067.4(FOXL2):c.338del (p.Ile113fs)	FOXL2	Pathogenic	criteria provided, single submitter
369909	NM_023067.4(FOXL2):c.353_476dup (p.His159fs)	FOXL2	Pathogenic	criteria provided, single submitter
369912	NM_023067.4(FOXL2):c.576dup (p.Lys193fs)	FOXL2	Pathogenic	criteria provided, multiple submitters, no conflicts
369914	NM_023067.4(FOXL2):c.582C>G (p.Tyr194Ter)	FOXL2	Pathogenic	criteria provided, single submitter
369915	NM_023067.4(FOXL2):c.612G>A (p.Trp204Ter)	FOXL2	Pathogenic	criteria provided, multiple submitters, no conflicts
369916	NM_023067.4(FOXL2):c.618del (p.Pro207fs)	FOXL2	Pathogenic	criteria provided, single submitter
369917	NM_023067.4(FOXL2):c.630_651dup (p.Cys218fs)	FOXL2	Pathogenic	criteria provided, single submitter
369918	NM_023067.4(FOXL2):c.632C>A (p.Ser211Ter)	FOXL2	Pathogenic	criteria provided, single submitter
369919	NM_023067.4(FOXL2):c.644A>G (p.Tyr215Cys)	FOXL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
369922	NM_023067.4(FOXL2):c.662_689del (p.Ala221fs)	FOXL2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FOXL2	Definitive	Autosomal dominant	blepharophimosis, ptosis, and epicanthus inversus syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FOXL2	Orphanet:572333	Blepharophimosis-ptosis-epicanthus inversus syndrome plus
FOXL2	Orphanet:572354	Blepharophimosis-ptosis-epicanthus inversus syndrome type 1
FOXL2	Orphanet:572361	Blepharophimosis-ptosis-epicanthus inversus syndrome type 2
FOXL2	Orphanet:99915	Malignant granulosa cell tumor of the ovary
COPB2	Orphanet:2512	Autosomal recessive primary microcephaly

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FOXL2	HGNC:1092	ENSG00000183770	P58012	Forkhead box protein L2	gencc,clinvar
COPB2	HGNC:2232	ENSG00000184432	P35606	Coatomer subunit beta'	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FOXL2	Forkhead box protein L2	Transcriptional regulator.
COPB2	Coatomer subunit beta'	The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Go…

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	8.6×	0.225
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FOXL2	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
COPB2	Scaffold/PPI	no		WD40_rpt, Beta-prop_COPA/B_2nd, WD40/YVTN_repeat-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
left ovary	1
ovary	1
parotid gland	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FOXL2	84	broad	marker	left ovary, stromal cell of endometrium, ovary
COPB2	295	ubiquitous	marker	parotid gland, stromal cell of endometrium, type B pancreatic cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COPB2	2,982
FOXL2	1,727

Intra-cohort edges

A	B	Sources
COPB2	FOXL2	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FOXL2	P58012	2
COPB2	P35606	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcriptional regulation of testis differentiation	1	356.9×	0.007	FOXL2
SUMOylation of transcription factors	1	285.5×	0.007	FOXL2
COPI-dependent Golgi-to-ER retrograde traffic	1	55.4×	0.018	COPB2
COPI-mediated anterograde transport	1	54.9×	0.018	COPB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
female somatic sex determination	1	8426.0×	0.001	FOXL2
granulosa cell differentiation	1	8426.0×	0.001	FOXL2
oocyte growth	1	2106.5×	0.003	FOXL2
positive regulation of luteinizing hormone secretion	1	1685.2×	0.003	FOXL2
extraocular skeletal muscle development	1	1404.3×	0.003	FOXL2
positive regulation of follicle-stimulating hormone secretion	1	1404.3×	0.003	FOXL2
embryonic eye morphogenesis	1	766.0×	0.004	FOXL2
apoptotic DNA fragmentation	1	601.9×	0.005	FOXL2
uterus development	1	401.2×	0.006	FOXL2
intra-Golgi vesicle-mediated transport	1	263.3×	0.008	COPB2
ovarian follicle development	1	195.9×	0.010	FOXL2
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	168.5×	0.011	COPB2
single fertilization	1	91.6×	0.018	FOXL2
anatomical structure morphogenesis	1	69.6×	0.022	FOXL2
endoplasmic reticulum to Golgi vesicle-mediated transport	1	68.0×	0.022	COPB2
intracellular protein transport	1	32.4×	0.042	COPB2
positive regulation of apoptotic process	1	28.4×	0.045	FOXL2
negative regulation of DNA-templated transcription	1	15.8×	0.076	FOXL2
cell differentiation	1	14.6×	0.077	FOXL2
positive regulation of DNA-templated transcription	1	14.0×	0.077	FOXL2
negative regulation of transcription by RNA polymerase II	1	8.9×	0.115	FOXL2
regulation of transcription by RNA polymerase II	1	5.8×	0.164	FOXL2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FOXL2	0	0
COPB2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
COPB2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	FOXL2, COPB2

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FOXL2	0	—
COPB2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.